Process for preparing polymer particles

ABSTRACT

A process is provided for preparing particles of polymer by heating the polymer having an inherent viscosity not exceeding about 0.6 dl/g when measured at a temperature of about 30° C. in chloroform or hexafluoroisopropanol, dividing the heated polymer into particles, and then solidifying these particles such that substantially no fibers are formed among the particles.

BACKGROUND OF THE INVENTION

This invention relates to a process for preparing particles of polymer,e.g., spheroidal particulates or beads of the bioabsorbable variety,employing various individual atomization techniques such as meltextrusion and/or rotary atomization. The particles are useful, interalia, in the repair of damaged or defective bone.

The medical use of polymer particles including those of thebioabsorbable variety are known, inter alia, from U.S. Pat. Nos.3,882,858; 4,535,485; 4,547,390; 4,643,735; and 4,663,447. There hasbeen an increase in interest in utilizing both bioabsorbable andnon-absorbable particles to facilitate bone or fibrous tissuerepair/reconstruction.

A number of processes are known for preparing finely divided polymericparticles, e.g., mechanical grinding, solvent precipitation, dispersion,and spray atomization of solutions or slurries. U.S. patent applicationSer. No. 654,219, filed Feb. 12, 1991, now U.S. Pat. No. 5,143,662describes producing particles of polymer by subjecting the polymer torotary atomization. In rotary atomization, the polymer is applied to arotation bell, cup or disk with mechanical forces predominating in thebreakup of the polymer into particles. U.S. patent application Ser. No.503,264, filed Apr. 2, 1990 and now U.S. Pat. No. 5,102,983 issued Apr.7, 1992 describes a process for preparing foamed, bioabsorbable polymerparticles by a freeze-drying technique.

Processes which form microspheres of absorbable material less than orequal to 0.2 mm in diameter for use in controlled release of drugs, arewell-known. Such spheres have generally been formed by a solventevaporation technique. Alternatively, polymeric microspheres, e.g.,beads, of average particle size greater than or equal to 0.2 mm indiameter can be formed by an emulsion polymerization process. Suchemulsion polymerization has been successfully utilized to form beads ofpolymethylmethacrylate and styrene.

For medical applications, it is often desirable to control not only theparticle size distribution of the polymeric particles but level offibers which are present as well.

SUMMARY OF THE INVENTION

The present invention is directed to a process for preparing particlesfrom a polymer having fiber-forming properties comprising:

a) heating a polymer having an inherent viscosity not exceeding about0.6 dl/g when measured at a temperature of about 30° C. in chloroform orhexafluoroisopropanol (HFIP);

b) dividing the thus-heated polymer into particles; and

c) solidifying the polymer particles,

such that substantially no fibers are formed among the solidifiedparticles.

When the conditions of the present invention are followed, particles ofpolymer of substantially uniform size, e.g., microspheres of about 0.1to about 3.0 mm average size (in diameter) can be prepared frompolymeric substances, while fiber forming tendencies of the polymer aresuppressed. In other words, the fiber forming tendency of the polymericmaterial, which is believed to relate to the surface tension exhibitedby the polymer, is inhibited according to the present invention suchthat substantially no fibers are produced among the particles that areprepared. As used herein, the term "fiber" refers to materials which maybe characterized as having a denier (see, e.g., Plastics Terms Glossary,Fourth Edition, Phillips Chemical Company, Bartlesville, Oklahoma).

The particles are preferably formed into spheres which can be used as apacking or molded part in dental or orthopedic applications in which abony defect is filled with material. Such material then acts as ascaffold for new bony ingrowth while, in the case of bioabsorbableparticles, being resorbed by the body, leaving behind a fully healedbone tissue structure.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be described in greater detail below, withreference to the accompanying drawings in which:

FIG. 1 is a perspective view of an extrusion die adapter which can beutilized in accordance with the present invention; and,

FIG. 2 is a perspective view of another extrusion die adapter which canbe utilized in accordance with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

In order to minimize the formation of fibers during the process of thepresent invention, a polymer is selected for processing which has aninherent viscosity not exceeding about 0.6 dl/g when measured at atemperature of about 30° C. in chloroform or HFIP (concentration of thepolymer during this measurement is about 0.25 g/dl). HFIP is generallyused as the measuring solvent when glycolide content exceeds about 40mole percent of the overall polymer being measured. Preferably, thepolymer has an inherent viscosity, when measured under these conditions,of about 0.2 to about 0.5 dl/g, more preferably about 0.25 to about 00.45 dl/g.

It should be noted that the polymer can have an initial inherentviscosity within the levels set forth above. Alternatively, the polymercan have an initial inherent viscosity exceeding about 0.6 dl/g whenmeasured under the above conditions and then can be treated, e.g.,heated, to cause degradation of the polymer, such as by hydrolysis (whenheated in the presence of moisture), to reduce the viscosity to thelevels set forth above. The polymer can then be further heated inaccordance with the heating step of the present invention.

While not being bound by any particular theory on physical properties,it is believed that the polymer possessing an inherent viscosity notexceeding about 0.6 dl/g when measured under the above conditions,exhibits a reduced tendency to form fibers because of a physicalattribute associated with the polymer, e.g., an increased surfacetension and/or reduced chain lengths of individual polymer chainsrelative to higher inherent viscosity materials. The inherent viscosityis a function of, among other factors, the molecular weight of apolymer. Accordingly, the inherent viscosity of the polymer can becontrolled by selecting a polymer having an appropriate molecularweight.

The polymer is preferably bioabsorbable and can be derived frompolyglycolic acid, glycolide, lactic acid, lactide, dioxanone,e-caprolactone, trimethylene carbonate, etc., and various combinationsof these and related monomers. Polymers of this type are known in theart, principally as materials for the fabrication of such surgicaldevices as sutures, wound clips, and the like, as disclosed, e.g., inU.S. Pat. Nos. 2,668,162; 2,703,316; 2,758,987; 3,225,766; 3,297,033;3,422,181; 3,531,561; 3,565,077; 3,565,869; 3,620,218; 3,626,948;3,636,956; 3,736,646; 3,772,420; 3,773,919; 3,792,010; 3,797,499;3,839,297; 3,867,190; 3,878,284; 3,982,543; 4,047,533; 4,060,089;4,137,921; 4,157,437; 4,234,775; 4,237,920; 4,300,565; and, 4,523,591;U.K. Patent No. 779,291; D. K. Gliding et al., "Biodegradable polymersfor use in surgery - - polyglycolic/poly(lactic acid) homo- andco-polymers: 1", Polymer, Volume 20, pages 1459-1464 (1979), and D. F.Williams (ed.), Biocompatibility of Clinical Implant Materials, Vol. II,ch. 9: "Biodegradable Polymers" (1981). Copolymers of glycolide andlactide with or without additional monomers are preferred and of theseglycolidelactide copolymers are most preferred.

The present invention may also be practiced on non-absorbable polymericmaterials having fiber-forming properties such as nylon, polyester,polypropylene, polytetrafluoroethylene (PTFE), polyethyleneterephthalate (Dacron), etc.

According to the present invention, the polymeric material is heated soas to produce a flowable mass. The polymer is preferably heated to atemperature from about 60° C. to about 300° C. More particularly, thetemperature to which the polymeric material will be heated, will dependon the melt characteristics of the polymer selected. For example, for aglycolide/lactide copolymer, the system is heated to a temperature offrom about 100° to about 300° C., preferably from about 170° C. to about270° C., and most preferably from about 220° C. to about 250° C. Forpolymers having lower melting points, e.g., polycaprolactone, lowertemperatures may be employed, e.g., about 60° C., whereas highertemperature may be required for materials having higher melting points.

After heating the polymer, the heated molten polymer is divided intoparticles with the molten particles then being solidified. The polymeris divided and solidified into the particles such that an averageparticle size (diameter) of the particles when solidified will be fromabout 0.1 to about 3 mm, more preferably from about 0.2 mm to about 1.5mm, and most preferably from about 0.3 to about 1.0 mm.

In this regard, the molten polymer can be divided, e.g., into droplets,by being extruded through a capillary provided in an extrusion die ofextrusion apparatus. Suitable extrusion apparatus which can be utilizedin accordance with the present invention are described in G. A. Kruder,"Extrusion", Encyclopedia of Polymer Science and Engineering (SecondEdition), Volume 6, pages 571-631, and in P. N. Richardson, "PlasticsProcessing", Encyclopedia of Chemical Technology (Third Edition), Volume18, pages 185-189. Any part of the extrusion apparatus such as theextruder screw or the capillary die can be heated to the appropriatetemperature in order to heat the polymer.

As the extrusion apparatus, an Instron Rheometer available from theInstron Corp. of Canton, Massachusetts 02021 can be used. The InstronRheometer has an extrusion barrel of about 20 cm³ capacity and which isprovided with a capillary die at the bottom thereof. The barrel isheated to the appropriate temperature and then loaded with the polymer,which is forced down through the capillary die by means of a plungerextending into the barrel.

Extrusion can be carried out through a capillary die adapter 1illustrated in FIG. 1, having a capillary 2 of substantially constantinner diameter h. Alternatively, a capillary die adapter 20 of FIG. 2can be utilized, which comprises a capillary 12 of narrowing innerdiameter. Rate of extrusion and diameter size of the capillary determineultimate particle size of solidified polymer particles. In particular,the capillary has a narrowest inner diameter of preferably about 0,010to about 0.002 inch, more preferably about 0.009 to about 0.003 inch,and most preferably about 0.008 to about 0.004 inch. The polymer isextruded through the capillary preferably at a rate of about 15 to about0.3 inch/min., more preferably at a rate of about 12 to about 0.5inch/min., and most preferably at a rate of about 10 to about 1inch/min.

Alternatively, the molten polymer can be divided into droplets, afterbeing heated, by being sprayed through a spray nozzle. The spray nozzleitself can be heated to an appropriate temperature level in order toheat the polymer.

Furthermore the polymer can also be divided, after heating, by beingapplied onto a rotary atomizer upon whose surface the polymer breaks upinto particles which are thrust away from the axis of the rotaryatomizer. Suitable rotary atomizers which can be utilized in accordancewith the present invention include those disclosed in U.S. Pat. Nos.4,256,677; 3,741,703; and 3,743,464. A circular rotating element, e.g. aspinning disk of the rotary atomizer, can be flat, convex, concave, oreven bell-shaped, and can contain protruding vanes on a surface thereof.

The size of the spinning disk itself and the rpm., i.e. rate ofrotation, can be interrelated to provide the optimum centrifugalacceleration for the formation of the particles of bioabsorbablepolymer. Variations of this centrifugal acceleration will affect theultimate size of the particles that are formed. The revolutions of thespinning disk are controlled within a range of preferably about 100 toabout 1000 rpm., more preferably within a range of about 130 to about850 rpm., and most preferably within a range of about 160 to about 700rpm. Furthermore, the disk itself is preferably between about 66 andabout 86 cm. in diameter, more preferably between about 71 and about 81cm. in diameter, and most preferably between about 75 and about 77 cm.in diameter. The instantaneous velocity of the disk is preferablycontrolled within a range of about 4 to about 40 m./sec., morepreferably within a range of about 5 to about 35 m./sec., and mostpreferably within a range of about 6 to about 28 m./sec.

The bioabsorbable polymer is supplied in the form of a thin film onto asurface of the spinning disk of the rotary atomizer, whereby thecentrifugal acceleration breaks the thin film into particles of thebioabsorbable polymer. Preferably, this film of polymer is applied about0.01 to about 3.5 mm. thick on the spinning disk, more preferably about0.1 to about 3.2 mm. thick, and most preferably of about 1.0 to about3.0 mm. thick. Surface tension will cause the resulting particles ofbroken up polymer to ultimately harden into particles which arespheroidal or in the shape of beads, as these particles are radiallydischarged from the disk, i.e. fall off the edge of the rotary spinningdisk of the rotary atomizer and are cooled. Varying the film thicknesson the spinning disk or varying the feed rate of the flowablebioabsorbable polymer affects particle size, with the thinnest filmcausing the smallest particles to be formed.

Clearly, the molten polymer can be divided by other means within thecontext of the present invention. Once divided, the molten particles ofpolymer are solidified. Solidification can be carried out by allowingthe extruded, sprayed or atomized particles to fall into a liquid whichis immiscible with the molten polymer, which freezes the polymerparticles on contact therewith, and in which the solidified polymer isnot soluble. The freezing liquid can be, e.g., liquid nitrogen, andmixtures of solid carbon dioxide and a liquid such as acetone, pentane,etc. In general, the temperature of the freezing liquid isadvantageously at least about 10° C. below the freezing temperature ofthe polymer particles. The lower the temperature of the freezing liquid,the faster the polymer particles will freeze solid therein. It isdesirable to maintain a certain particle configuration, e.g., spheresupon freezing, and therefore rapid, even instantaneous freezing iscalled for. This can be conveniently achieved employing a freezingliquid such as liquid nitrogen.

The particles of frozen polymer can be recovered from the freezingliquid employing any suitable means, e.g., draining, straining,filtering, decanting or centrifuging, and the like. This operation isconducted at or below the melting point of the frozen polymericparticles to maintain the particles in the frozen state.

Alternatively, the polymeric particles can be solidified by fallingfreely through the air. The particles are allowed to fall a distance ofat least about 40 cm. through the air, whereby the particles aresufficiently cooled before striking a collecting unit so that theparticles will not stick together upon striking the collecting unit.More specifically, the particles are allowed to fall a distance ofpreferably about 190 to about 254 cm., more preferably about 200 toabout 240 cm., and most preferably about 215 to about 230 cm. beforestriking the collecting unit. The collecting unit may be provided, e.g.,as disclosed in U.S. Pat. Nos. 4,256,677 and 3,743,464.

The particles or beads formed of bioabsorbable or non-absorbablepolymers can be used as filler in a surgical prosthesis, i.e. forimplantation in a cavity provided in bone or fibrous tissue to encourageregrowth and regeneration of the tissue. The particles of thebioabsorbable polymer are absorbed by the body at a predictable rateallowing tissue or bony ingrowth as absorption takes place. The rate ofabsorption is characteristic of the polymer utilized. Thus, e.g., aglycolide-lactide copolymer will often completely resorb within sixmonths in contrast to about two years for polyglycolide homopolymer.Both the bioabsorbable and nonabsorbable polymeric particles are readilymolded to fill cavities or other contours. The beads can be heated tosoftening temperature, e g, to about 60° C., at which temperature theycan be worked and shaped.

Any required drug, medicinal material, or growth factor can beincorporated into the polymer prior to processing, e.g. by addition tothe polymer in the customary amounts so that at the conclusion of thepolymeric particle manufacturing process herein, the particles willcontain a predetermined amount of one or more of such substances.

Thus, it is within the scope of this invention to incorporate one ormore medico-surgically useful substances into the particles, e.g., thosewhich accelerate or beneficially modify the healing process whenparticles are applied to a surgical repair site. For example, thepolymer particles can carry a therapeutic agent which will be depositedat the repair site. The therapeutic agent can be chosen for itsantimicrobial properties, capability for promoting repair orreconstruction and/or new tissue growth or for specific indications suchas thrombosis. Antimicrobial agents such as broad spectrum antibiotics(gentamicin sulphate, erythromycin or derivatized glycopeptides) whichare slowly released into the tissue can be applied in this manner to aidin combating clinical and sub-clinical infections in a tissue repairsite.

To promote repair and/or tissue growth, one or several growth promotingfactors can be introduced into the particles, e.g., fibroblast growthfactor, bone growth factor, epidermal growth factor, platelet derivedgrowth factor, macrophage derived growth factor, alveolar derived growthfactor, monocyte derived growth factor, magainin, and so forth. Sometherapeutic indications are: glycerol with tissue or kidney plasminogenactivator to cause thrombosis, superoxide dismutase to scavenge tissuedamaging free radicals, tumor necrosis factor for cancer therapy orcolony stimulating factor and interferon, interleukin-2 or otherlymphokine to enhance the immune system.

The present invention will be explained in greater detail, by way of thefollowing examples:

EXAMPLE 1

A capillary die adapter 1 of FIG. 1 having the following dimensions:D=0.730 inch; L₁ =1/8 inch; L₂ =1/8 inch; d=0.300 inch; and h=0.016inch, was provided on a barrel of an Instron Rheometer extrusionapparatus. The extrusion apparatus, including the barrel and the adapter1, was heated to 250° C. and then loaded with 25/75 mole percentglycolide/lactide copolymer having an inherent viscosity, measured at30° C. in HFIP and at a concentration of 0.25 g/dl, of 0.49 dl/g. Thiscopolymer was maintained in the barrel of the extrusion apparatus for 5minutes and then extruded through capillary 2 of the die adapter 1 at arate of 0.3 inch/min., whereby droplets of the polymer were formed.These droplets of the polymer were allowed to fall from the die adapter1 a distance of 40 cm. and into a vat of liquid nitrogen at atemperature of -196° C., with the droplets of polymer therebysolidifying into beads. The beads were collected from the liquidnitrogen, classified, and were found to have an average diameter of 3mm. The solidified polymer thus formed was substantially free of fibers.

This procedure was repeated, but with the 25/75 mole percentglycolide/lactide copolymer being exposed to air for 72 hours beforebeing added to the heated extruder barrel. Clearer beads of a range ofparticle size of 2.8-3.1 mm were produced, the solidified polymer beingsubstantially free of fibers.

EXAMPLE 2

The procedure of Example 1 was repeated, but with a die adapter disc 10of FIG. 2 having a capillary 12 necking down from an inner entrancediameter D' of 1.25 mm to an inner exit diameter d' of 0.008 inch, withthe extrusion apparatus including the adapter 10 being heated to atemperature of 225° C., and with respective rates of extrusion of 1inch/min., 3 inch/min., and 10 inch/min. respectively for equal extrudedamounts of the 25/75 mole percent glycolide/lactide copolymer having aninherent viscosity of 0.5 dl/g measured at 30° C. in HFIP and at aconcentration of 0.25 g/dl. The extrudate formed a stream that brokeinto droplets upon exiting from the adapter 10, with the fallingdroplets being directed into a bucket of liquid nitrogen at -296° C.with stirring. A total of 15.65 g of beads (the product beingsubstantially fiber free) was collected from these three combined runsand then classified, with the distribution being reported in Table IIbelow:

                  TABLE II                                                        ______________________________________                                                  Weight (g) of Particles                                                                       % of Particles                                      Sieve No.*                                                                              Retained Thereon                                                                              Retained Thereon                                    ______________________________________                                        14                7.29               46.58                                    16                4.23               27.03                                    18                2.25               14.38                                    20                0.72               4.60                                     25                0.63               4.02                                     40                0.53               3.39                                               Total   15.65 g  Total     100.00%                                  ______________________________________                                         *a No. 14 sieve has openings of 1.41 mm;                                      a No. 16 sieve has openings of 1.19 mm;                                       a No. 18 sieve has openings of 1.00 mm;                                       a No. 20 sieve has openings of 0.841 mm;                                      a No. 25 sieve has openings of 0.707 mm; and                                  a No. 40 sieve has openings of 0.420 mm.                                 

EXAMPLE 3

The procedure of Example 2 was repeated but with all molten polymerbeing extruded at a rate of 1 inch/min. A total of 6.96 g of beads wascollected and then classified, with the distribution being reported inTable III below:

                  TABLE III                                                       ______________________________________                                                    Weight (g) of Particles                                                                       % Particles                                       Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        14                   0.84             12.07                                   16                   1.71             24.57                                   18                   1.99             28.59                                   20                   1.83             26.29                                   25                   0.25             3.59                                    40                   0.30             4.31                                    Passed Through 40    0.04             0.58                                                Total    6.96 g   Total   100.00%                                 ______________________________________                                    

EXAMPLE 4

The procedure of Example 2 was repeated, but with all molten polymerbeing extruded at a rate of 3 inches/min. A total of 13.03 g of beadswas collected and then classified, with the distribution being reportedin Table IV below:

                  TABLE IV                                                        ______________________________________                                                    Weight (g) of Particles                                                                       % Particles                                       Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        14                   9.93             76.21                                   16                   2.30             17.65                                   18                   0.64             4.91                                    20                   0.06             0.46                                    25                   0.07             0.54                                    40                   0.02             0.15                                    Passed Through 40    0.01             0.08                                                Total    13.03 g  Total   100.00%                                 ______________________________________                                    

EXAMPLE 5

The procedure of Example 2 was repeated, but with all molten polymerbeing extruded at a rate of 10 inches/min. A total of 19.62 g of beadswas collected and then classified, with the distribution being reportedin Table V below:

                  TABLE V                                                         ______________________________________                                                    Weight (g) of                                                                 Particles    % Particles                                          Sieve No.   Retained Thereon                                                                           Retained Thereon                                     ______________________________________                                        14                  13.49          68.76                                      16                  3.38           17.23                                      18                  1.35           6.88                                       20                  0.63           3.21                                       25                  0.38           1.94                                       40                  0.32           1.63                                       Passed Through 40   0.07           0.36                                                   Total   19.62 g  Total 100.01%**                                  ______________________________________                                         **100.01% value due to rounding of significant figures.                  

EXAMPLE 6

The procedure of Example 3 was repeated in its entirety, but with themolten polymer being extruded through die adapter 10 having an extrusionchannel 12 necking down from an entrance diameter D' of 1.25 mm to aminimum a diameter d' of 0.006 inch at the outlet thereof. A total of5.94 g of beads was collected and then classified, with the distributionbeing reported in Table VI below:

                  TABLE VI                                                        ______________________________________                                                    Weight (g) of Particles                                                                       % Particles                                       Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        14                   0.70             11.78                                   16                   1.09             18.35                                   18                   1.45             24.41                                   20                   1.17             19.70                                   25                   0.88             14.82                                   40                   0.58             9.76                                    Passed Through 40    0.07             1.18                                                Total    5.94 g    Total  100.00%                                 ______________________________________                                    

EXAMPLE 7

The procedure of Example 4 was repeated in its entirety, but with themolten polymer being extruded through die adapter 10 having an extrusionchannel 12 necking down from an entrance diameter D' of 1.25 mm to aminimum diameter d' of 0.006 inch at the outlet thereof. A total of 8.49g of beads was collected and then classified, with the distributionbeing reported in Table VII below:

                  TABLE VII                                                       ______________________________________                                                    Weight (g) of Particles                                                                       % Particles                                       Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        14                   2.58             30.39                                   16                   2.89             34.04                                   18                   2.15             25.32                                   20                   0.39             4.59                                    25                   0.23             2.71                                    40                   0.18             2.12                                    Passed Through 40    0.07             0.83                                                Total    8.49 g   Total   100.00%                                 ______________________________________                                    

EXAMPLE 8

The procedure of Example 5 was repeated in its entirety, but with themolten polymer being extruded through a die adapter 10 having anextrusion channel 12 necking down from an entrance diameter D' of 1.25mm to a minimum diameter d' of 0.006 inch at the outlet thereof. A totalof 14.5 g of beads was collected and then classified, with thedistribution being reported in Table VIII below:

                  TABLE VIII                                                      ______________________________________                                                    Weight (g) of Particles                                                                       % Particles                                       Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        14                   5.63             38.83                                   16                   5.06             34.90                                   18                   1.52             10.48                                   20                   0.72             4.96                                    25                   0.82             5.66                                    40                   0.63             4.34                                    Passed Through 40    0.12             0.83                                                Total    14.50 g  Total   100.00%                                 ______________________________________                                    

EXAMPLE 9

The procedure of Example 2 was repeated in its entirety, but with themolten polymer additionally being stirred before extrusion. A total of56.77 g of beads was collected and then classified, with thedistribution being reported in Table IX below:

                  TABLE IX                                                        ______________________________________                                                    Weight (g) of Particles                                                                       % of Particles                                    Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        14                   22.36           39.39                                    16                   17.00           29.95                                    18                   11.78           20.75                                    20                   1.99            3.51                                     25                   1.66            2.92                                     40                   1.62            2.85                                     Passed Through 40    0.36            0.63                                                 Total    56.77 g  Total  100.00%                                  ______________________________________                                    

EXAMPLE 10

The procedure of Example 2 was repeated in its entirety, but with a die10 having a channel 12 necking down from an entrance diameter D' of 1.25mm to a minimum exit diameter d' of 0.006 inch. A total of 7.61 g ofbeads was collected and then classified, with the distribution beingreported in Table X below:

                  TABLE X                                                         ______________________________________                                                    Weight (g) of Particles                                                                       % Particles                                       Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        20                   0.32            4.20                                     25                   3.72            48.88                                    40                   3.39            44.55                                    Passed Through 40    0.18            2.37                                                 Total    7.61 g   Total  100.00%                                  ______________________________________                                    

EXAMPLE 11

The procedure of Example 7 was repeated in its entirety, but withpolyglycolic acid (PGA), having an inherent viscosity of 0.25 dl/gmeasured at 30° C. in HFIP and at a concentration of 0.25 g/dl, beingheated to 225° C. and then being extruded at a rate of 3 inch/min. Atotal of 10.04 g of PGA beads was collected and then classified, withthe distribution being reported in Table XI below:

                  TABLE XI                                                        ______________________________________                                                    Weight (g) of Particles                                                                       % Particles                                       Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        20                   6.30            62.75                                    25                   1.80            17.93                                    40                   1.70            16.93                                    Passed Through 40    0.24            2.39                                                 Total    10.04 g  Total  100.00%                                  ______________________________________                                    

EXAMPLE 12

The procedure of Example 11 was repeated, but with the polyglycolic acid(PGA) being heated to 240° C. and then being extruded (the PGA had aninherent viscosity of 0.25 dl/g at 30° C. in HFIP and at a concentrationof 0.25 g/dl). A total of 5.52 g of PGA beads was collected and thenclassified, with the results being reported in Table XII below:

                  TABLE XII                                                       ______________________________________                                                    Weight (g) of Particles                                                                       % Particles                                       Sieve No.   Retained Thereon                                                                              Retained Thereon                                  ______________________________________                                        20                   4.90            88.77                                    25                   0.22            3.98                                     40                   0.31            5.62                                     Passed Through 40    0.09            1.63                                                 Total    5.52 g   Total  100.00%                                  ______________________________________                                    

What is claimed is:
 1. Process for preparing particles of bioabsorbablepolymer, comprising:a) heating to a temperature from about 60° to about300° C., a polymer derived from monomers selected from the groupconsisting of glycolic acid, lactic acid, dioxanone, e-caprolactone andtrimethylene carbonate and having an inherent viscosity between about0.5 and about 0.6 dl/g when measured at a temperature of about 30° C. inchloroform or hexafluoroisopropanol, to form a molten or flowable mass;b) dividing the molten or flowable mass of thus-heated polymer intoparticles; and c) solidifying the thus-divided particles to formsolidified polymer particles of average particle size of about 0.1 toabout 3 mm; whereby substantially no fibers are formed among thesolidified particles.
 2. The process of claim 1, wherein the polymer hasan initial inherent viscosity not exceeding about 0.6 dl/g when measuredat the temperature of about 30° C. in chloroform orhexafluoroisopropanol.
 3. The process of claim 1, wherein the polymerhas an initial inherent viscosity above about 0.6 dl/g when measured ata temperature of about 30° C. in chloroform or hexafluoroisopropanol,and further comprising:treating the polymer so that the viscosity of thepolymer is reduced to a level not exceeding about 0.6 dl/g when measuredat 30° C. in chloroform or hexafluoroisopropanol and then heating thepolymer in accordance with step (a).
 4. The process of claim 3, whereinthe polymer is treated by heating to cause the polymer to degrade. 5.The process of claim 4, wherein the polymer is heated in the presence ofmoisture to cause hydrolysis.
 6. The process of claim 1, wherein thepolymer is divided by extrusion through a capillary.
 7. The process ofclaim 6, wherein the capillary has a minimum diameter from about 0.010to about 0.002 inch.
 8. The process of claim 7, wherein the minimumcapillary diameter is from about 0.009 to about 0.003 inch.
 9. Theprocess of claim 8, wherein the minimum capillary diameter is from about0.008 to about 0.004 inch.
 10. The process of claim 6, wherein thepolymer is extruded through the capillary at a rate of about 15 to about0.3 inch/min.
 11. The process of claim 10, wherein the extrusion rate isabout 12 to about 0.5 inch/min.
 12. The process of claim 11, wherein theextrusion rate is about 10 to about 1 inch/min.
 13. The process of claim1, wherein the polymer is divided by being sprayed through a nozzle. 14.The process of claim 1, wherein the polymer particles are solidified bybeing introduced into a liquid which is immiscible with the polymer andwhich freezes the polymer particles on contact therewith.
 15. Theprocess of claim 14, wherein the solidified polymer particles areinsoluble in the liquid.
 16. The process of claim 1, wherein the polymerparticles are solidified by falling freely through air.
 17. The processof claim 1, wherein the particles fall a distance of at least about 40cm. through the air.
 18. The process of claim 1, wherein the averageparticle size of the solidified particles is from about 0.2 to about 1.5mm.
 19. The process of claim 18, wherein the average particle size ofthe solidified particles is from about 0.3 to about 1.0 mm.
 20. Theprocess of claim 1, wherein the average particle size of the solidifiedparticles is equal to or greater than about 0.42 mm.
 21. The process ofclaim 1, wherein the polymer is heated to a temperature of from about100° to about 300° C.
 22. The process of claim 21, wherein the polymeris heated to a temperature of from about 170° to about 270° C.
 23. Theprocess of claim 22, wherein the polymer is heated to a temperature offrom about 220° to about 250° C.
 24. A process for preparing particlesof bioabsorbable polymer, comprising:a) heating to a temperature of fromabout 60° to about 300° C., a polymer derived from monomers selectedfrom the group consisting of glycolic acid, lactic acid, dioxanone,e-caprolactone and trimethylene carbonate and having an inherentviscosity between about 0.5 and about 0.6 dl/g when measured at atemperature of about 30° C. in chloroform or hexafluoroisopropanol toform a molten or flowable mass; b) dividing the molten or flowable massof thus-heated polymer into particles, wherein the polymer is divided bybeing applied onto a rotary atomizer upon whose surface the moltenpolymer breaks up into particles which are thrust away from the axis ofthe rotary atomizer; and c) solidifying the thus-divided particles toform solidified polymer particles of average particle size of about 0.1to about 3 mm; whereby substantially no fibers are formed among thesolidified particles.
 25. The process of claim 24, wherein the averageparticles size of the solidified particles is equal to or greater thanabout 0.42 mm.
 26. A process for preparing particles of bioabsorbablepolymer, comprising:a) heating to a temperature from about 60° to about300° C., a polymer derived from monomers selected from the groupconsisting of glycolic acid, lactic acid, dioxanone, e-caprolactone andtrimethylene carbonate and having an inherent viscosity between about0.2 and about 0.6 dl/g when measured at a temperature of about 30° C. inchloroform or hexafluoroisopropanol, to form a molten or flowable mass;b) dividing the molten or flowable mass of thus-heated polymer intoparticles; and c) solidifying the thus-divided particles by introducingthe particles into a liquid which is immiscible with the polymer andwhich freezes the polymer particles on contact therewith, the liquidbeing selected from the group consisting of liquid nitrogen, andmixtures of solid carbon dioxide and a liquid, to form solidifiedpolymer particles of average particle size of about 0.1 to about 3 mm;whereby substantially no fibers are formed among the solidifiedparticles.
 27. Process for preparing particles of bioabsorbable polymer,consisting essentially of the steps of:a) heating to a temperature fromabout 60° to about 300° C., a polymer derived from monomers selectedfrom the group consisting of glycolic acid, lactic acid, dioxanone,e-caprolactone and trimethylene carbonate and having an inherentviscosity between about 0.5 and about 0.6 dl/g when measured at atemperature of about 30° C. in chloroform or hexafluoroisopropanol, toform a molten or flowable mass; b) dividing the molten or flowable massof thus-heated polymer into particles; and c) solidifying thethus-divided particles to form solidified polymer particles of averageparticle size of about 0.42 to about 3 mm; wherein substantially nofibers are formed among the solidified particles.